Phosphorylation of IGF-IR/InsR is elevated in ERα+ breast cancer cells resistant to estrogen deprivation and tamoxifen, possibly due to increased secretion of IGF1/2 in these cells and elevated expression of retinoblastoma-binding protein 2 that inhibits IGFBP4/5 by interacting with ER-NRIP1-HDAC1 complex [107–109]. This evidence concerns the gene INSR and breast cancer.